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31.
The effect of tertiary basic drugs on mitochondrial MAO activity and the effect of MAO inhibitors (MAOIs) on basic drug accumulation in the isolated perfused rat lung were studied to clarify the role of MAO in drug binding to lung tissue. In the perfused lung preparation, the inhibition of MAO by basic drugs correlated well with their lipid solubilities and followed competitive kinetics. The inhibitory rank order (imipramine
diphenhydramine > quinine > metoclopramide > procainamide) also correlated with their accumulation in the perfused lung. Moreover, MAOI treatment decreased the accumulation of basic drugs in the lung, and the potency of MAOIs to inhibit drug accumulation in the lung correlated with their MAO inhibitory activity. These results indicate that lung MAO has specific binding sites for basic drugs and may function as a drug reservoir. 相似文献
32.
Kawabata K 《Pathology, research and practice》1999,195(11):781-786
Paraganglionic tissues incidentally observed in the gallbladder are presented. The patients, a 51- and a 55-year-old woman, underwent gallbladder resection for chronic cholecystitis with gallstones. Two and one paraganglionic tissues were observed in the subserosal connective tissue of the two gallbladders, respectively. Immunohistochemically, the chief cells were positive for chromogranin A, and the sustentacular cells were positive for S100 protein. Tyrosine hydroxylase (in two of three), dopamine beta-hydroxylase (in one of three), methionine-enkephalin (in two of three), and leucine-enkephalin (in two of three) were also positive in a small amount of the chief cells. These structures, which slightly resembled adrenal medulla or retroperitoneal paraganglia, might be misunderstood as an infiltration of primary or metastatic carcinoma into the subserosal connective tissue. 相似文献
33.
Proteinase activated receptor 2: Role of extracellular loop 2 for ligand-mediated activation 总被引:2,自引:0,他引:2
Al-Ani B Saifeddine M Kawabata A Hollenberg MD 《British journal of pharmacology》1999,128(5):1105-1113
1. Rat proteinase-activated receptor-2 (PAR2) variants were stably expressed in rat KNRK cells: (a) wild-type (wt) - PAR2; (b) PAR2PRR, with the extracellular loop 2 (EL-2) sequence P231E232E233mutated to PRR and (c) PAR2NET, with the EL-2 sequence, PEEV changed to NETL. Cell lines were evaluated for their sensitivity (calcium signalling) towards trypsin and the receptor-activating peptides, SLIGRL-NH2, SLIGEL-NH2, trans-cinnamoyl(tc)-LIGRLO-NH2, and SFLLR-NH2. 2. SLIGEL-NH2 exhibited low potency (1 : 200 relative to SLIGRL-NH2) in wild-type PAR2. Its activity was increased 5 fold in PAR2PRR, but it was inactive in PAR2NET. 3. In PAR2PRR, the potencies of SLIGRL-NH2, tc-LIGRLO-NH2, and SFLLR-NH2 were decreased by 80 - 100 fold. But, the potency of trypsin was decreased by only 7 fold. 4. In PAR2NET, highly homologous in EL-2 with proteinase-activated receptor-1 (PAR1), the potency of the PAR1-derived peptide, SFLLR-NH2, was reduced by 100 fold compared with wt-PAR2, whereas the potency of the PAR2-derived AP, SLIGRL-NH2 was reduced 10 fold. In contrast, the potency of trypsin in PAR2NET was almost the same as in wt-PAR2. 5. We conclude that the acidic EL-2 tripeptide, PEE, in PAR2 plays an important role in governing agonist activity. 6. The data obtained with the PEEV-->NETL mutation suggested: (a) that SLIGRL-NH2 and SFLLR-NH2 interact in a distinct manner with PAR2 and (b) that SFLLR-NH2 may interact differently with PAR2 than it does with PAR1. 7 The differential reductions in the potencies of SLIGRL-NH2, compared with trypsin in the PAR2PRR and PAR2NET cell lines point to differences between the interactions of the trypsin-revealed tethered ligand and the free receptor-activating peptide with PAR2. 相似文献
34.
Y Watanabe K Hatano Y Matsumoto S Tawara H Yamamoto K Kawabata H Takasugi F Matsumoto S Kuwahara 《The Journal of antibiotics》1999,52(7):649-659
The in vitro activity of FK041, a new orally active cephem antibiotic, against a wide variety of clinical isolates of bacteria was investigated and compared with those of cefdinir (CFDN) and cefditoren (CDTR). FK041 exhibited broad spectrum activity against reference strains of Gram-positive and Gram-negative aerobes and anaerobes. FK041 was active against clinical isolates of Gram-positive organisms except Enterococcus faecalis with MIC90s less than 1.56 microg/ml. FK041 was more active than CFDN and CDTR against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae and was comparable to CFDN and CDTR against Streptococcus pyogenes and Streptococcus pneumoniae. FK041 had no activity against methicillin-resistant staphylococci, like CFDN and CDTR. FK041 showed moderate activity against penicillin-resistant S. pneumoniae with an MIC range of 0.05 approximately 3.13 microg/ml, and was superior to CFDN but inferior to CDTR. Against clinical isolates of many Gram-negative organisms such as Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, FK041 had good activity comparable or superior to those of CFDN and CDTR. However, it was inferior to CDTR in activity against Moraxella catarrhalis, Haemophilus influenzae, Morganella morganii, and Serratia marcescens, and was inactive against Pseudomonas aeruginosa. With FK041 a small difference between MIC and MBC against S. aureus, E. coli, K. pneumoniae, and H. influenzae was found, indicating that its action is bactericidal against these species. FK041 was stable to group 2beta-lactamase hydrolysis but was unstable to group 1beta-lactamase hydrolysis. The stability of FK041 to these enzymes was similar to those of CFDN and CDTR. FK041 showed high affinity for the main penicillin-binding proteins (PBPs) of S. aureus (PBP 3, 2, and 1) and E. coli (PBP 3, 4, lbs, 2, and 1a). 相似文献
35.
Yusuke Demizu Kazufumi Kagawa Yasuo Ejima Hideki Nishimura Ryohei Sasaki Toshinori Soejima Toshihiro Yanou Masakazu Shimizu Yoshiya Furusawa Yoshio Hishikawa Kazuro Sugimura 《Radiotherapy and oncology》2004,71(2):207-211
We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray. 相似文献
36.
37.
18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer. 总被引:9,自引:0,他引:9
Ryohei Sasaki Ritsuko Komaki Homer Macapinlac Jeremy Erasmus Pamela Allen Kenneth Forster Joe B Putnam Roy S Herbst Cesar A Moran Donald A Podoloff Jack A Roth James D Cox 《Journal of clinical oncology》2005,23(6):1136-1143
PURPOSE: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. RESULTS: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs (= 5.0) showed significantly better DFS rates than those with high SUVs (> 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs (= 5.0) indicated a significantly better DFS than those with high SUVs (> 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy. 相似文献
38.
Minami T Okazaki J Kawabata A Kawaki H Okazaki Y 《Environmental toxicology and pharmacology》1996,2(4):316-326
The relationship between the accumulation of platinum in the cerebral cortex following cisplatin administration and injury to the blood-brain barrier after lipopolysaccharide (LPS) treatment was investigated. The appearance of intravenously injected fluorescein in the brain was significantly increased 10–24 h after LPS treatment, the effect being dose-dependent. Platinum was detectable in the cerebral cortex of cisplatin-treated mice 24 h after LPS treatment, but not without LPS treatment. In mice pretreated with -tocopherol, LPS administration did not significantly augment fluorescein penetration into the brain, whereas pretreatment with either allopurinol or ascorbic acid did not modify the LPS-induced increase in fluorescein penetration. In contrast, platinum in the cerebral cortex after cisplatin administration was still detectable in the allopurinol-, ascorbic acid-, and -tocopherol-pretreated groups, and the levels of platinum in these groups were not significantly different from those in the group treated with LPS only. Administration of superoxide dismutase (SOD), but not of catalase, tended to inhibit the penetration of fluorescein. Both SOD and catalase significantly lowered platinum content in the cerebral cortex following cisplatin administration in mice treated with LPS. Thus, free radicals may injure the blood-brain barrier in mice challenged with LPS, and allow cisplatin to penetrate into the cerebral cortex, resulting in platinum accumulation. 相似文献
39.
Koji Nakajima Hirohito Kubota Itaru Kato Kiyotaka Isobe Hiroo Ueno Kagehiro Kozuki Kuniaki Tanaka Naoko Kawabata Takashi Mikami Kosuke Tamefusa Ritsuo Nishiuchi Satoshi Saida Katsutsugu Umeda Hidefumi Hiramatsu Souichi Adachi Junko Takita 《Cancer science》2022,113(7):2472
Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A‐rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A‐MLLT3‐rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A‐MLLT3‐rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre‐post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia. 相似文献
40.
Shinya Komori Katsumi Hirose Mariko Sato Akihiko Takeuchi Ryohei Kato Tomoaki Motoyanagi Takaomi Harada Yuhei Yamazaki Mayumi Harada Yuki Narita Takahiro Kato Yoshihiro Takai 《Journal of radiation research》2022,63(4):684
The dosimetric effect of set-up error in boron neutron capture therapy (BNCT) for head and neck cancer remains unclear. In this study, we analyzed the tendency of dose error by treatment location when simulating the set-up error of patients. We also determined the tolerance level of the set-up error in BNCT for head and neck cancer. As a method, the distal direction was shifted with an interval of 2.5 mm, from 0.0 mm to +20.0 mm and compared with the dose at the reference position. Similarly, the horizontal direction and vertical direction were shifted, with an interval of 5.0 mm, from −20.0 mm to +20.0 mm. In addition, cases with 3.0 mm and 5.0 mm simultaneous shifts in all directions were analyzed as the worst-case scenario. The dose metrics of the minimum dose of the tumor and the maximum dose of the mucosa were evaluated. From unidirectional set-up error analysis, in most cases, the set-up errors with dose errors within ±5% were Δdistal < +2.5 mm, Δhorizontal < ±5.0 mm and Δvertical < ±5.0 mm. In the simulation of 3.0 mm shifts in all directions, the errors in the minimum tumor dose and maximum mucosal dose were −3.6% ±1.4% (range, −5.4% to −0.6%) and 2% ±1.4% (range, 0.4% to 4.5%), respectively. From these results, if the set-up error was within ±3.0 mm in each direction, the dose errors of the tumor and mucosa could be suppressed within approximately ±5%, which is suggested as a tolerance level. 相似文献